Serum Levels of IL-22 in Patients with Oral Lichen Planus and Cutaneous Lichen Planus

Statement of the Problem: Lichen planus disease is a chronic inflammatory disorder of mucosal and cutaneous tissues with yet unclear etiology and pathogenesis. Cytokines play an important role in the initiation, maintenance of inflammatory and intercellular crosstalk. Purpose: We assessed serum levels of IL-22 in patients with oral and cutaneous lichen planus and made comparison with healthy individuals. Materials and Method: In this case-control study, peripheral blood samples of 40 patients with lichen planus disease, included two groups of oral lichen planus (n=20) and cutaneous lichen planus (n=20) were compared with 32 healthy individuals in this case-control study. Serum samples were prepared from patients with lichen planus and IL-22 concentration was measured in each serum sample by using a commercial ELISA Kit. The obtained data were then analyzed using the Kruskal-Wallis (one-way ANOVA) test. Results: The IL-22 serum levels were significantly higher in patients with oral lichen planus compared to the healthy control group (p< 0.001). No statistically significant differences were observed in serum levels of IL-22 in cutaneous lichen planus patients compared to the controls (p= 0.183). Conclusion: Increased IL-22 serum levels in patients with oral lichen planus may play an important role in the pathogenesis of oral lichen planus. The administration of the recombinant or antagonist of IL-22 could be a new therapeutic opportunity in the treatment of oral lichen planus.


Introduction
Lichen planus (LP) is a chronic and T cell-mediated inflammatory disorder of the skin and mucous membranes, which is classified based on the tissue involved, such as oral lichen planus (OLP), cutaneous lichen planus (CLP) and oral-cutaneous lichen planus [1][2].
LP affects about 0.5-2% of the general population, especially females, and most often occurs in middle age [3]. LP lesions can be symptomless, annular, linear, hypertrophic, atrophic, bullous, ulcerative, and pigmented [4]. Clinically, CLP is characterized by purple, polygonal, pruritic papules frequently covered by Wickham striae, located on the flexor surface, of the wrist, the shins, the trunk, and the medial thighs [5]. A basic clinical diagnosis of OLP can be made by Wickham striae [6].
It is reported that 0.4% to 5.3% of OLP lesions are transformed into carcinoma, making it a pre-malignant condition [7]. The etiology and pathogenesis of LP is unclear, but the combination of mast cell degranulation and matrix and matrix metalloproteinase activation in OLP lesions leads to T cell accumulation in the superficial lamina propria, basal membrane disruption, intraepithelial T cell migration, and keratinocyte apoptosis [8].
The majority of infiltering immune cells into epithelial layer and lamina propria are CD8+T and CD4+T cells, respectively [8][9] . Local and systemic inducers of cellmediated hypersensitivity, autoimmune responses to   epithelial antigens, viral infections, some systemic med-ications, dental material, stress, genetics, and tobacco chewing have been reported to be the triggering factors for OLP [10][11].
Cytokines play an important role in recruitment, differentiation, and activation of immune cells into inflammatory sites. Cytokines are soluble proteins with a low molecular weight that are produced by various cells, which play a complex role in the initiation, progression, and regression of autoimmune inflammation [12]. They regulate the immune responses by binding to cell surface receptors. IL-22 is a member of IL-10 superfamily that uses IL-22R1/IL-10R2 for cell signaling in target cells, produced by Th17, Th22, NK, innate lymphoid cells and various types of CD4+ and CD8+ T lymphocytes [13].
IL-22 plays an important role in immune responses, par ticularly in inflammatory and autoimmune diseases in humans and animals [19]. IL-22 might have a protective, regenerative, or pathogenic role depending on the disease stage [20][21][22].
Several authors [34][35][36] have suggested that different cytokines play a role in the initiation and progression of oral lichen planus. Hence, identifying and introducing appropriate immunological targets for diagnostic and therapeutic usage is essential. IL-22 plays a key role in mucosal barrier defense, tissue repair, survival, and proliferation of epithelial cells, but evidence demonstrated both the protective and the pathogenic properties of IL-22 in autoimmune disease, infection, and malignancy [37]. In the current study, we scrutinized if the IL-22 serum level was different in LP in different forms such as OLP and CLP. Therefore, we measured IL-22 levels in patients' sera with OLP and CLP in comparison with healthy controls.

Materials and Method
In this study, 20 OLP patients and 20 CLP patients were Furthermore, participants were asked if they smoked cigarette, use any drugs, had a history of any surgery, infectious diseases, vaccination, trauma, immune therapy, and chemotherapy. All individuals with items listed above and those with a history of allergy, autoimmunity, immunodeficiency, and cancer were excluded. The control group included 32 healthy individuals who were selected from healthy blood donors in the same age range and gender. Informed consent was obtained from all participants before blood donation and data publication.

Sampling
Approximately 5 ml of peripheral blood samples were collected from each participant, and the sera were separated in 3500 rpm for 10 min, stored at -20 º C until

Discussion
LP is a chronic autoimmune disease that leads to epithe- IL-22 has both protective and pathogenic roles in different diseases and showed inconsistent results in several studies [38][39][40]. Furthermore, IL-22 is involved in the  [21], and skin diseases [41] but has protective, anti-apoptotic and anti-inflammatory effects in graft versus host disease [23], rheumatoid arthritis [24], and asthma [25].
Previous studies also reported significantly increased IL-22 levels in oral biopsies from patients with OLP compared with the normal controls [42][43]. Besides, the IL-22 level was increased in the lesions of OLP patients, but its level in the serum was inconsistent [33].

Conflict of Interests
The authors have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.